Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/119450
Title: STRESS RESPONSE IN CELLS AND MICE LACKING GADD34, AN ESSENTIAL COMPONENT OF STRESS-ACTIVATED EIF2α PHOSPHATASE
Authors: TAY SU LING, ANGELINE (ZHENG SHULING, ANGELINE)
Keywords: ER stress, UPR, GADD34, eIF2α phosphatase
Issue Date: 24-Mar- 15
Source: TAY SU LING, ANGELINE (ZHENG SHULING, ANGELINE) (0015-03-24). STRESS RESPONSE IN CELLS AND MICE LACKING GADD34, AN ESSENTIAL COMPONENT OF STRESS-ACTIVATED EIF2α PHOSPHATASE. ScholarBank@NUS Repository.
Abstract: Endoplasmic reticulum (ER) stress plays a key role in chronic human diseases including cancer, diabetes, heart disease and neurodegeneration. In response to ER stress, the translation initiation factor, eIF2a, is rapidly phosphorylated by an ER transmembrane kinase, PERK. This attenuates global protein synthesis and reduces the protein load, the source of stress, in the ER. The protein encoded by the growth arrest and DNA damage-inducible transcript 34 (GADD34) binds protein phosphatase 1 and catalyzes the dephosphorylation of eIF2a, promoting recovery from translational repression. To date, GADD34, whose levels are transcriptionally elevated by ER stress, was thought to function solely in a negative feedback loop that promotes cell recovery from stress. However, we discovered that Gadd34 mRNA was constitutively expressed and highly translated in early stages of ER stress. Moreover, GADD34 generate a stress-activated eIF2a phosphatase well before the activation of the Gadd34 gene. Our studies showed that GADD34 was critical for the translation of mRNAs encoding stress genes and progression of the stress response. Challenging Gadd34-/- mice with an ER stress-inducing drug, tunicamycin, highlighted that the delayed stress response protected mouse tissues from apoptosis following chronic ER stress. These data provided support for the use of small molecule GADD34 inhibitors in treatment of chronic human diseases.
URI: http://scholarbank.nus.edu.sg/handle/10635/119450
Appears in Collections:Ph.D Theses (Open)

Show full item record
Files in This Item:
File Description SizeFormat 
TayASL.pdf4.82 MBAdobe PDFView/Download

Page view(s)

88
checked on Nov 17, 2017

Download(s)

9
checked on Nov 17, 2017

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.